ライフサイエンスコーパス: HSCR

1 HSCR is caused by the developmental failure of ENS proge

2 HSCR may be inherited as a single gene disorder with red

3 HSCR mutations have been identified in the RET receptor

4 ormed de novo mutation (DNM) screening on 24 HSCR trios.

5 uencing of SEMA3A, SEMA3C, and SEMA3D in 254 HSCR-affected subjects followed by in silico protein str

6 o haplotype sharing was evident in any of 36 HSCR kindreds typed for microsatellite markers surroundi

7 es of these variants in 997 samples from 376 HSCR families of European ancestry, that significant gen

8 present a trans-ethnic meta-analysis of 507 HSCR cases and 1191 controls, combining all published GW

9 Importantly, for a majority of patients in a HSCR cohort, the myenteric ganglia from the ganglionated

10 We identified one familial mutation in a HSCR patient with a known de novo RET mutation and malro

11 ived reinduction chemotherapy before HDT and HSCR.

12 Four patients received two cycles of HDT and HSCR.

13 these unique systems and in diseases such as HSCR and CAKUT.

14 se chemotherapy (HDT) followed by autologous HSCR.

15 later in development and which might not be HSCR-associated.

16 tor tyrosine kinase have been shown to cause HSCR.

17 tor tyrosine kinase have been shown to cause HSCR.

18 leagues identify a new mechanism that causes HSCR-like disease in mice and involves deposition of exc

19 alence of continuous ventilatory dependence, HSCR, and neural crest tumors was seen in the nonpolyala

20 euroblastoma (NB) with Hirschsprung disease (HSCR) (aganglionosis of the terminal bowel) and congenit

21 Hirschsprung disease (HSCR) demonstrates a complex pattern of inheritance with

22 The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET.

23 ionosis reminiscent of Hirschsprung disease (HSCR) in humans.

24 Hirschsprung disease (HSCR) is a common congenital disorder that results in in

25 The Hirschsprung disease (HSCR) is a complex congenital disorder, arising from abn

26 Hirschsprung disease (HSCR) is a complex disorder that exhibits incomplete pen

27 Hirschsprung disease (HSCR) is a human congenital disorder, defined by the abs

28 Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in whi

29 Hirschsprung disease (HSCR) is a multigenic neurocristopathy clinically recogn

30 Hirschsprung disease (HSCR) is a multigenic, congenital disorder that affects

31 Hirschsprung disease (HSCR) is a partially penetrant oligogenic birth defect t

32 The risk of Hirschsprung disease (HSCR) is approximately 15/100 000 live births per newbor

33 Hirschsprung disease (HSCR) is caused by a reduction of enteric neural crest c

34 evidence suggests that Hirschsprung disease (HSCR) is the consequence of multiple gene interactions t

35 Hirschsprung disease (HSCR) is the most common cause of neonatal intestinal ob

36 ) mice, an established Hirschsprung disease (HSCR) model, on distinct inbred backgrounds, C57BL/6J (B

37 Clinical expression of Hirschsprung disease (HSCR) requires the interaction of multiple susceptibilit

38 binding and increasing Hirschsprung disease (HSCR) risk 4-fold.

39 dentified a regulatory Hirschsprung disease (HSCR) susceptibility variant.

40 is segmentally lost in Hirschsprung disease (HSCR), a consequence of cell-autonomous and non-autonomo

41 lon, commonly known as Hirschsprung disease (HSCR), is the most frequent cause of congenital bowel ob

42 Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most

43 Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most

44 Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a rela

45 Hirschsprung disease (HSCR), the most common hereditary cause of intestinal ob

46 Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, res

47 an disorders including Hirschsprung disease (HSCR).

48 a hallmark feature of Hirschsprung disease (HSCR).

49 ionosis reminiscent of Hirschsprung disease (HSCR).

50 Hirschsprung disease (HSCR, MIM #142623) is a multigenic neurocristopathy (neu

51 Hirschsprung's disease (HSCR) causes functional intestinal obstruction due to th

52 Hirschsprung's disease (HSCR) is a severe congenital anomaly of the enteric nerv

53 the colon results in Hirschsprung's disease (HSCR) or colonic aganglionosis.

54 n in humans known as Hirschsprung's disease (HSCR).

55 pment is relevant to Hirschsprung's disease (HSCR; congenital aganglionosis of the terminal bowel), w

56 The distribution of RET variants in diverse HSCR patients suggests a "cellular-recessive" genetic mo

57 For almost every HSCR gene, incomplete penetrance of the HSCR phenotype h

58 in group I families is sufficient to explain HSCR inheritance, a genome scan reveals a new susceptibi

59 ying these mutations should be evaluated for HSCR and neural crest tumors.

60 clinically relevant pathogenic mechanism for HSCR that involves cell-autonomous changes in ECM compos

61 e report the generation of a mouse model for HSCR--named Holstein--that contains an untargeted transg

62 re normal has guided surgical procedures for HSCR patients.

63 t to establish a possible link between human HSCR and mutations affecting the Gdnf locus, we studied

64 to the variable aganglionosis seen in human HSCR families.

65 onic segment, and sex bias observed in human HSCR patients.

66 olon hypoganglionosis, which resembles human HSCR.

67 st that GDNF is a minor contributor to human HSCR susceptibility and that loss of its function in ent

68 One of the primary genes affected in HSCR encodes the G protein-coupled endothelin receptor-B

69 we review studies evaluating ENS defects in HSCR and non-HSCR mouse models, concluding with clinical

70 No evidence of linkage was detected in HSCR kindreds and no mutations were found in patients.

71 No evidence of linkage was detected in HSCR kindreds, and no sequence variants were found to be

72 or could be involved in sexual dimorphism in HSCR.

73 thereby contributing to sexual dimorphism in HSCR.

74 t 12 different genes have been identified in HSCR patients but the complex pattern of inheritance and

75 ption factor, SOX10, have been identified in HSCR patients.

76 our attention on the enhancer implicated in HSCR to demonstrate that this element drives reporter ex

77 elin receptor type B (EDNRB) are involved in HSCR pathogenesis; however, also important in ENS develo

78 ecursors rescue disease-related mortality in HSCR mice (Ednrb(s-l/s-l)), although the mechanism of ac

79 embryos, it does not play an obvious role in HSCR.

80 system consistent with its proposed role in HSCR.

81 Studies in HSCR families have identified RET-dependent modifiers fo

82 patients after surgery as well as studies in HSCR mouse models suggest that aberrant NC segregation a

83 f HSCR and suggest a mechanism for increased HSCR incidence in children with Down syndrome (trisomy 2

84 r data open new fields of investigation into HSCR pathology and provide novel insights into the devel

85 To determine whether known HSCR susceptibility loci are acting as modifiers of Sox1

86 R), but epistatic effects in long-segment (L-HSCR) and syndromic cases have not been fully explained.

87 DNRB, EDN3 and SOX10 lead to long-segment (L-HSCR) and syndromic HSCR but fail to explain the transmi

88 he DNMs we identified occur in RET, the main HSCR gene, and the remaining 20 DNMs reside in genes not

89 enotypic expression by studying 12 multiplex HSCR families.

90 entilation syndrome (CCHS) (also known as NB-HSCR-CCHS), linked to mutations in PHOX2B.

91 udies evaluating ENS defects in HSCR and non-HSCR mouse models, concluding with clinical implications

92 throughout the length of the intestine (non-HSCR) have also found that certain genetic alterations a

93 We identify and validate novel HSCR genes using whole exome sequencing (WES), burden te

94 However, 80% of HSCR patients have short-segment Hirschsprung disease (S

95 mental in the identification and analysis of HSCR disease genes.

96 er insights into the genetic architecture of HSCR and has profound implications for future study desi

97 S development and suggest that some cases of HSCR may be preventable.

98 r, GDNF has been implicated in rare cases of HSCR.

99 congenital origin, the molecular etiology of HSCR remains elusive for >70% of patients.

100 in mice models many of the early features of HSCR.

101 and up to one-third of the sporadic forms of HSCR.

102 try individuals, is involved in all forms of HSCR.

103 supporting its crucial role in all forms of HSCR; however, coding sequence mutations are present in

104 type B (EDNRB) are central to the genesis of HSCR.

105 ome of the so-called missing heritability of HSCR and suggest a mechanism for increased HSCR incidenc

106 The inheritance of HSCR is complex, often non-Mendelian and characterized b

107 Another mouse model of HSCR disease, Dom, arose spontaneously at the Jackson La

108 ll mutant ENS precursors enable modelling of HSCR-related migration defects, and the identification o

109 In 2 different mouse models of HSCR, addition of mycophenolate increased the penetrance

110 As such, the gene at 9q31 is a modifier of HSCR penetrance.

111 Loss-of-function mutations of HSCR genes and haploinsufficiency of their gene products

112 d the gene for mutations in a large panel of HSCR patients.

113 nned for GFRA1 mutations in a large panel of HSCR patients.

114 ith a predisposition for the pathogenesis of HSCR.

115 atures of the complex inheritance pattern of HSCR.

116 protein haploinsufficiency and promotion of HSCR development, thereby contributing to sexual dimorph

117 risk allele, rs9282834 increases the risk of HSCR from 1.1 to 26.7.

118 together, make contributions to the risk of HSCR.

119 candidate genes for human genetic studies of HSCR.

120 pigmentary anomalies typical of a subset of HSCR patients categorized as Waardenburg-Shah syndrome (

121 Subsets of HSCR individuals also present with neural crest-derived

122 d drug-based strategies for the treatment of HSCR.

123 that persist after the surgical treatment of HSCR.

124 ols, combining all published GWAS results on HSCR to fine-map these loci and narrow down the putative

125 ontinued gastric dysmotility in postsurgical HSCR patients.

126 s have short-segment Hirschsprung disease (S-HSCR), which has not been associated with genetic factor

127 f the much more common short-segment form (S-HSCR).

128 ependent modifiers for short-segment HSCR (S-HSCR), but epistatic effects in long-segment (L-HSCR) an

129 dissection why the inheritance pattern of S-HSCR is nonmendelian.

130 Here we show oligogenic inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers

131 mutation in RET) and from 2 patients with S-HSCR (without a RET mutation), as well as RET(+/-) and R

132 e conducted a genome scan in families with S-HSCR and identified susceptibility loci at 3p21, 10q11 a

133 e searched for mutation(s) associated with S-HSCR by combining genetic and transcriptome data from pa

134 ught to identify mutations associated with S-HSCR, and used the clustered regularly interspaced short

135 tion in the vinculin gene (VCL M209L) with S-HSCR.

136 dentified mutations in VCL associated with S-HSCR.

137 ed RET-dependent modifiers for short-segment HSCR (S-HSCR), but epistatic effects in long-segment (L-

138 In addition, a splice isoform-specific HSCR missense mutation, which does not inactivate the RE

139 lead to long-segment (L-HSCR) and syndromic HSCR but fail to explain the transmission of the much mo

140 SOX10 mutations contribute to syndromic HSCR cases and Sox10 alleles in mice exhibit aganglionos

141 , disrupted expression of both Sox10 and the HSCR disease gene Ednrb in Dom mutant embryos, and loss

142 Recent studies identified over half of the HSCR disease susceptibility genes as targets for the sex

143 very HSCR gene, incomplete penetrance of the HSCR phenotype has been observed, probably due to geneti

144 Thus, HSCR has become a model of a complex polygenic disorder

145 c and nongenetic factors have been linked to HSCR, the underlying mechanisms that prevent ENS precurs

146 isposition of patients with Down syndrome to HSCR.

147 Genetic defects underlie HSCR, but much of the variability in the occurrence and

148 g variants in 13 genes are known to underlie HSCR risk, with the most frequent variants in the ret pr

149 dies that have searched for genes underlying HSCR have focused on ENS-related pathways and genes not

150 Knowledge of the genetics underlying HSCR is incomplete, particularly genes that control cell

151 pic classes with defined risks to understand HSCR etiology.

152 We screened 106 unrelated HSCR patients for mutations in GDNF by direct sequencing

153 cyte deficiencies (Hirschsprung-Waardenburg, HSCR-WS, MIM #277580).

154 One of the genes associated with HSCR is endothelin receptor type B (Ednrb).

155 in intron 1 is significantly associated with HSCR susceptibility and makes a 20-fold greater contribu

156 related transcription factor associated with HSCR, in the Ednrb ENS enhancer, and mutational analyses

157 Our results suggest that HDT with HSCR is an effective treatment for patients with Wilms'

158 candidate disease gene for individuals with HSCR whose disease does not have an identified genetic o

159 ene are frequently detected in patients with HSCR, mutations in the gene encoding its ligand (glial c